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The evolution of genetic networks by non-adaptive processes

Key Points

  • Raises questions about the widespread belief that the structures of genetic networks are driven entirely by adaptive processes.

  • Provides an overview of the empirical evidence for the evolution of novel regulatory mechanisms by neutral processes with little or no alteration at the phenotypic level.

  • Provides a simple explanation, on the basis of amounts of intergenic DNA, of why multicellular species are more prone to the evolution of complex regulatory mechanisms than are unicellular species.

  • Demonstrates that the effective size of a population alone can dictate the potential pathways of network evolution.

  • Demonstrates that recombinational activation, and not mutational masking, is a powerful force for promoting redundant genetic pathways.

  • Argues that models of network evolution that ignore intermediate states of population-level variation are incapable of providing meaningful insight into issues of pathway evolution.

Abstract

Although numerous investigators assume that the global features of genetic networks are moulded by natural selection, there has been no formal demonstration of the adaptive origin of any genetic network. This Analysis shows that many of the qualitative features of known transcriptional networks can arise readily through the non-adaptive processes of genetic drift, mutation and recombination, raising questions about whether natural selection is necessary or even sufficient for the origin of many aspects of gene-network topologies. The widespread reliance on computational procedures that are devoid of population-genetic details to generate hypotheses for the evolution of network configurations seems to be unjustified.

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Figure 1: A model for the recruitment of an upstream activator B.
Figure 2: The likelihood of alternative modes of gene regulation depends strongly on the relative rates of loss and gain of transcription-factor binding sites.
Figure 3: A consideration of the pairs of recombinant progeny for all pairs of alternative parental regulatory states reveals the recombinational advantage of redundantly regulated alleles.
Figure 4: Recombination encourages the evolution of redundantly regulated alleles.
Figure 5: Average frequencies of several alternative three-gene network configurations under the assumptions of complete linkage of the DNA-level elements involved in the activation of gene A.
Figure 6: Average frequencies of the three most common three-gene network configurations in large, recombining populations.
Figure 7: Expected null distributions of node density (number of transcription factors that actually interact with downstream gene A).

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Acknowledgements

I am very grateful to E. Haag, M. Hahn and three anonymous reviewers for helpful comments. This work has been supported by US National Science Foundation and US National Institutes of Healthe grants to the author.

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Glossary

Effective population size

A scaled measure of the size of a natural population that is relevant to population genetics. This value is equivalent to the size of the idealized, random-mating population that gives equivalent allele-frequency dynamics, and is generally one or more orders of magnitude smaller than the actual population size.

Power-law distribution

A distribution for a variable x that follows the form axb.

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Lynch, M. The evolution of genetic networks by non-adaptive processes. Nat Rev Genet 8, 803–813 (2007). https://doi.org/10.1038/nrg2192

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